Malke Horst, Ferretti Joseph J
Oklahoma University Health Sciences Center, Department of Microbiology and Immunology, Oklahoma City, OK 73190, USA.
J Med Microbiol. 2007 Jun;56(Pt 6):707-714. doi: 10.1099/jmm.0.46984-0.
In an attempt to expand the available knowledge of pathogen-host interactions during ex vivo growth of Streptococcus pyogenes (GAS) in nonimmune whole human blood, the extents to which the expression of 51 genes including regulators with known targets, established virulence factors, physiologically important transporters and metabolic enzyme genes was differentially affected in the presence or absence of a functional codY gene were determined. The results obtained by quantitative real-time PCR using the M49 strain NZ131 showed that CodY influenced GAS gene activity in a dynamic fashion, with differential responses detected for 26 genes and occasionally characterized by discordance in the blood environment compared to laboratory medium. Degenerate derivatives of the recently discovered CodY box potentially serving as a cis-regulatory element for CodY action were identified in the upstream regions of 15 genes of the NZ131 genome, and these genes featured sequence motifs identical to the NZ131 CodY box in all completely sequenced S. pyogenes genomes. As none of these genes represented a genuine virulence factor, it seems likely, therefore, that the observed differential transcription of the majority of virulence genes was caused by indirect actions of CodY as part of a regulatory network.
为了扩大化脓性链球菌（GAS）在非免疫全人血中体外生长期间病原体-宿主相互作用的现有知识，确定了包括具有已知靶点的调节因子、既定毒力因子、生理上重要的转运蛋白和代谢酶基因在内的51个基因的表达在有无功能性codY基因的情况下受到不同影响的程度。使用M49菌株NZ131通过定量实时PCR获得的结果表明，CodY以动态方式影响GAS基因活性，检测到26个基因有不同反应，与实验室培养基相比，在血液环境中偶尔表现出不一致。在NZ131基因组的15个基因的上游区域鉴定出最近发现的可能作为CodY作用顺式调节元件的CodY框的简并衍生物，并且这些基因在所有完全测序的化脓性链球菌基因组中具有与NZ131 CodY框相同的序列基序。由于这些基因均不代表真正的毒力因子，因此，观察到的大多数毒力基因的差异转录似乎是由CodY作为调节网络一部分的间接作用引起的。
